Differential Adverse Renal Effects With Dapagliflozin, Empagliflozin in T2D

Renal harm in patients with type 2 diabetes.
Renal harm in patients with type 2 diabetes.
A comprehensive systematic review analyzes whether specific sodium-glucose cotransporter 2 inhibitors were more likely to be associated with adverse renal events in patients with type 2 diabetes.

Patients with type 2 diabetes (T2D) treated with a sodium-glucose cotransporter 2 (SGLT2) inhibitor were more likely to have an increased risk of adverse renal events when taking dapagliflozin compared with patients taking empagliflozin, according to a systematic review of randomized controlled trials recently published in the Diabetes, Obesity and Metabolism journal.

“There has been an increased risk [of] harm effects on renal function in patients taking dapagliflozin while empagliflozin appeared to have renal protective effects,” Yiqing Song, MD, ScD, from the department of epidemiology at the Richard M. Fairbanks School of Public Health, Indiana University, in Indianapolis, and colleagues wrote in their study.

Dr Song and colleagues performed a systematic review of 1334 composite renal events in 39,741 patients from 58 trials and 511 cases of acute renal impairment or failure in 36,716 patients from 53 trials listed in PubMed, EMBASE, CENTRAL, and ClinicalTrials.gov databases.

Patients were included in the analysis if they received a SGLT2 inhibitor for treatment of T2D that resulted in an adverse renal event.

The researchers found a significant association between patients taking dapagliflozin for T2D and composite renal events compared with patients in the placebo group (odds ratio [OR] = 1.64; 95% CI, 1.26-2.13), according to a network meta-analysis.

Patients taking empaglilflozin showed a significantly lower risk for composite renal events compared with placebo (OR = 0.63; 95% CI, 0.54-0.72).

Regarding adverse events, patients taking empaglilflozin had fewer adverse events compared with patients taking canagliflozin (OR = 0.48; 95% CI, 0.29-0.82) or dapagliflozin (OR = 0.38; 95% CI, 0.28-0.51).

When analyzing acute renal impairment or failure, patients taking empagliflozin showed a significantly lower risk (OR = 0.72; 95% CI, 0.60-0.86) compared with patients in the placebo group.

“Evidence showed that elevated serum creatinine or lowered [estimated glomerular filtration rate] eGFR returned to baseline levels more frequently in patients treated with dapagliflozin than with a comparator after a few months of therapy or when therapy was discontinued,” Dr Song and colleagues wrote.

“These findings indicated that abnormal changes in eGFR or creatinine during dapagliflozin therapy might reflect a temporary and reversible change in renal function, possibly caused by hemodynamic changes related to osmotic diuresis, reduction in blood pressure, or altered intrarenal hemodynamics.”

The researchers noted that future data should be collected in real-world settings and through other randomized controlled trials to verify their results.

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Tang H, Li D, Zhang J, et al. Sodium–glucose cotransporter 2 inhibitors and risk of adverse renal outcomes among type 2 diabetes patients: a network and cumulative meta-analysis of randomized controlled trials. Diabetes Obes Metab. 2017; doi:10.1111/dom.12917.